Why not introducing the third dimension in photodynamic therapy research?

Photodynamic therapy (PDT) is a clinically approved procedure for the treatment of diseases characterized by uncontrolled cell proliferation, particularly cancer. It involves the administration of a photosensitizer (PS) that is able to produce reactive oxygen species (ROS) upon irradiation with light, leading to the selective killing of neoplastic cells. A major challenge in PDT is the development of new PSs and drug-delivery systems that improve therapy efficacy and selectivity. To succeed in drug screening, it is crucial to use cellular systems that precisely reproduce the phenotype of the target tissue in order to obtain reliable biomedical data that correlate with in vivo tests. In this way, three-dimensional (3D) cultures are particularly attractive since they integrate chemical and mechanical signals that arise from extracellular matrix (ECM) and adjacent cells. Importantly, 3D models can mimic in vivo gene expression pattern and molecular gradients. These features significantly affect the outcome of PDT, enhancing the predictive power of 3D models. Therefore, PDT research should rely on the exploitation of this third dimension, guaranteeing a custom-tailor design depending on the tissue to be modeled, an easy applicability and reproducibility. The review summarizes progress in this emerging area.